1-Bromo-3,4,5-trifluorobenzene → 6-(6-Bromo-2,3,4-trifluorophenyl)-3,3-dimethylpiperidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-bromo-3,4,5-trifluorobenzene (313 mg, 1.48 mmol) in THF (3 mL) at −78° C. was added tert-butyllithium (1.74 mL of a 1.7 M solution in pentane, 2.96 mmol) dropwise. The reaction mixture was stirred for 1 h at −78° C., 3 h at 0° C., and then cooled back down to −78° C. A solution of benzyl (SS)-5-[(tert-butylsulfinyl)imino]-2,2-dimethylpentanoate (250 mg, 0.741 mmol, described in Intermediate 3) in toluene (5 mL) was added. The reaction mixture was stirred for 20 min at −78° C., 16 h at ambient temperature, and 1 h at reflux. The solvent was removed in vacuo and the crude solid dissolved in DMSO (5 mL). The crude product was purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=337 (M+1).

Provenance & Evidence